Severe bone loss
Severe bone loss is a common occurrence in metastatic cancer and current statistics indicate that bone is in fact the third most common site of metastasis of solid tumors. Osteolytic lesions are frequent in breast, lung and kidney cancer and almost all patients with multiple myeloma have extensive bone destruction. This increased bone resorption is responsible for a number of disabling features including intractable bone pain at the site of the metastasis, pathological fractures, nerve compression syndromes, and hypercalcemia when bone destruction is advanced. The current drugs help to control mild bone degradation but they unfortunately exhibit no impact on patients’ survival. Alethia is developing inhibitors of bone degradation by focusing on the discovery of new regulators of the activity of osteoclasts, the cells responsible for degrading the bone.
Alethia researchers applied an innovative target discovery and validation platform to generate subtracted cDNA libraries from mouse and human osteoclasts. Exhaustive expression profiling was performed to emphasize those targets whose expression was weak or absent in most normal tissues. In parallel, cell-based validation experiments were conducted to identify the genes required for osteoclast differentiation. This combined effort led to the assembly of a diversified portfolio of validated targets that are specifically expressed in differentiating osteoclasts. Alethia’s lead pipeline product in this indication is a mAb against AB-0326, a cell-surface protein that is stimulated by RANK ligand very early in osteoclast differentiation.
